Funding is requested to continue and enhance support of the inter- departmental center at Vanderbilt and its program, which is oriented towards augmenting research projects in several molecular aspects of toxicology. The Center in Molecular Toxicology functions through several units and core facilities, including Center Investigators, Director's Office, Clerical/Administrative, Cell Biology, Molecular Genetics, Nuclear Magnetic Resonance Spectroscopy, Mass Spectrometry/Analytical Chemistry, Protein Chemistry, and Pilot Projects. These units provide portions of salary support for the nine named Center Investigators and are intended to support ongoing research projects of Center Investigators by providing key instrumental facilities and expertise (as opposed to direct research project support, with the exception of Pilot Projects). In addition to the cadre of named Center investigators, a sizeable number of other faculty at Vanderbilt also work in related projects an contribute to provide an environment to foster research in toxicology, carcinogenesis, and environmental health. A training program with separate sources of funding also continues to operate. Mechanisms are in place for the regular internal and external review of individual and core programs. The Center brings together scientists interested in toxicology and having expertise in structural, synthetic, mechanistic chemistry, and bio-organic chemistry, mycology, enzymology, metal toxicology, biochemical regulation, cell culture, immunochemistry, chromatin structure, spectroscopy and separation chemistry, DNA-chemical interactions, chemical carcinogenesis, drug toxicity, and DNA repair. Major areas of research include interactions of metals with biological systems, the mechanisms and roles of biological oxidations, chemical-DNA interactions as they relate to genetic damage, and events related to receptor-ligand interactions. The research continues to be oriented toward the general goals of (1) understanding phenomena of toxicological interest in chemical terms, (2) answering questions related to toxicity at the biochemical level, and (3) applying such chemical and biochemical knowledge to problems involving human health.